• He S Yang, Sabrina E Racine-Brzostek, Mohsen Karbaschi, Jim Yee, Alicia Dillard, Peter A D Steel, William T Lee, Kathleen A McDonough, Yuqing Qiu, Thomas J Ketas, Erik Francomano, P J Klasse, Layla Hatem, Lars Westblade, Heng Wu, Haode Chen, Robert Zuk, Hong Tan, Roxanne C Girardin, Alan P Dupuis, Anne F Payne, John P Moore, Melissa M Cushing, Amy Chadburn, and Zhen Zhao.
• Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; NewYork-Presbyterian Hospital/Weill Cornell Medical Campus, New York, NY, USA.
• Biosens Bioelectron. 2021 Apr 15; 178: 113008.

AbstractThe association of mortality with the early humoral response to SARS-CoV-2 infection within the first few days after onset of symptoms (DAOS) has not been thoroughly investigated partly due to a lack of sufficiently sensitive antibody testing methods. Here we report two sensitive and automated testing-on-a-probe (TOP) biosensor assays for SARS-CoV-2 viral specific total antibodies (TAb) and surrogate neutralizing antibodies (SNAb), which are suitable for clinical use. The TOP assays employ an RBD-coated quartz probe using a Cy5-Streptavidin-polysacharide conjugate to improve sensitivity and minimize interference. Disposable cartridges containing pre-dispensed reagents require no liquid manipulation or fluidics during testing. The TOP-TAb assay exhibited higher sensitivity in the 0-7 DAOS window than a widely used FDA-EUA assay. The rapid and automated TOP-SNAb correlated well with two well-established SARS-CoV-2 virus neutralization tests. The clinical utility of the TOP assays was demonstrated by evaluating early antibody responses in 120 SARS-CoV-2 RT-PCR positive adult hospitalized patients. Higher TAb and SNAb positivity rates and more robust antibody responses at patient's initial hospital presentation were seen in inpatients who survived COVID-19 than those who died in the hospital. Survival analysis using the Cox Proportional Hazards Model showed that patients who had negative TAb and/or SNAb at initial hospital presentation were at a higher risk of in-hospital mortality. Furthermore, TAb and SNAb levels at presentation were inversely associated with SARS-CoV-2 viral load based on concurrent RT-PCR testing. Overall, the sensitive and automated TAb and SNAb assays allow the detection of early SARS-CoV-2 antibodies which associate with mortality.Copyright © 2021 Elsevier B.V. All rights reserved.

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